The invention relates to a method for collecting particles which are suspended in a liquid, in particular for collecting suspended biological objects, such as biological cells for example, in a fluidic microsystem. The invention also relates to a device for implementing such a method and to the uses thereof.
It is known to trap or collect particles which are suspended in a liquid in fluidic Microsystems in a dielectrophoretic field cage (see, for example, the publication “Trapping in AC octopole field cages” by T. Schnelle et al. in “Journal of Electrostatics”, vol. 50, 2000, pages 17 to 29). This technique has the disadvantage that only relatively large particles with typical dimensions >500 nm can reliably be trapped. In the case of smaller particles, such as viruses for example, the dielectrophoretic trapping forces may be too low or may be superposed by thermal distortions.
Using planar electrodes to which high-frequency AC voltages are supplied, electrohydrodynamic flows can be generated in a liquid-filled compartment by means of electroosmosis. In the publication “Optimizing Particle Collection for enhanced surface-based biosensors” (see “IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE”, November/December 2003, page 68), K. F. Hoettges et al. describe the use of circulating electrohydrodynamic flows to collect particles which are suspended in the liquid. In this method, as shown in FIG. 9, suspended particles 1′, 2′ are collected in a compartment 10′ having a lateral surface 11′. At the edges of electrodes 21′ (partially shown), which are arranged on the lateral surface 11′, an eddy flow 30′ is produced which circulates about an axis 31′ parallel to the orientation of the lateral surface 11′. A region where the flow is calm is formed in the centre of the electrodes 21′, which region represents a collecting area 40′ for the particles brought between the electrodes 21′ by the eddy flow 30′.
The technique described by K. F. Hoettges et al. has a number of disadvantages, in particular with regard to use in biology, biochemistry and medicine. The circulating eddy flow has a relatively small catchment area for the particles to be collected. Furthermore, the particles can be collected only immediately next to the electrodes. However, contact with the electrodes may be harmful for the particles, particularly if the particles comprise biological materials. Moreover, electrodes with a relatively large surface area are required in order to form suitably large collecting areas. However, undesirable heating occurs on electrodes with a large surface area. Finally, one significant disadvantage of the technique described by Hoettges et al. lies in the fact that said technique is based on electroosmosis and positive electrophoresis and therefore is restricted to low frequencies and low conductivities of the solutions used. It is therefore not possible to use this method to investigate cells in physiological solutions.
It is also known to guide viruses 1′ into the trapping area of a funnel-shaped, dielectric field cage 50′ by using electrohydrodynamic flows 30′, as shown in FIG. 10 (see the publication “Trapping of Viruses in High Frequency Electric Field Cages” by T. Schnelle et al. in “Naturwissenschaften” vol. 83, 1996, pages 172 to 176; the publication “High Frequency Electric Fields for Trapping of Viruses” by T. Müller et al. in “Biotechnology Techniques” vol. 10, 1996, pages 221 to 226; and the publication “Trapping of micrometer and sub-micrometer particles by high frequency electric fields and hydrodynamic forces” by T. Müller et al. in “J. Phys. D: Appl. Phys.” vol. 29, 1996, pages 340 to 349). Also in this technique there is the disadvantage that the collecting flow only collects viruses in the immediate vicinity of the electrodes 21′ used to form the field cage 50′ and therefore has a relatively small catchment area. Moreover, said method is restricted to low conductivities or low-salt solutions and is therefore also not suitable for investigating cells in physiological solutions.
Flows in fluidic Microsystems can also be induced by high electric field strengths (electric heating). However, this principle, which is used for example in traveling wave pumps in microchips (see the publication “A travelling-wave micropump for aqueous solutions: Comparison of 1 g and μg results” by T. Müller et al. in “Electrophoresis”, vol. 14, 1993, pages 764 to 772), may be disadvantageous for biological particles in particular, due to the conversion of heat.
The objective of the invention is to provide improved methods for collecting particles which are suspended in a liquid, in particular for collecting suspended biological objects, by means of which the disadvantages of the conventional methods are overcome and which in particular permit collection from a larger catchment area and without harm to the collected particles. Another objective of the invention is to provide improved devices for collecting particles which are suspended in a liquid, in particular for implementing the methods according to the invention.